ramipril and Acute-Kidney-Injury

Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines.. The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care.. We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used.. We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2.. This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury.

Topics: Acute Kidney Injury; Adverse Drug Reaction Reporting Systems; Amlodipine; Amphotericin B; Australia; Case-Control Studies; Ciprofloxacin; Diclofenac; Furosemide; Humans; Ibuprofen; Metformin; Naproxen; Omeprazole; Primary Health Care; Ramipril; Simvastatin; Spironolactone; Sulfamethoxazole; Telmisartan; Trimethoprim; Valacyclovir; Zoledronic Acid

Acute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn't been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats.. Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out.. Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group.. The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Disease Models, Animal; Glycerol; Inflammation Mediators; Oxidative Stress; Ramipril; Rats; Renin

Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is known that the antihypertensive drug hydralazine has demethylating activity, and that its optimum demethylating activity occurs at concentrations below blood pressure-lowering doses. Administration of low-dose hydralazine effectively induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter demethylation subsequently attenuated renal fibrosis and preserved excretory renal function independent of its blood pressure-lowering effects. In comparison, RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not detected upon administration of the angiotensin-converting enzyme inhibitor Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression.

Topics: Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Animals; CpG Islands; Dioxygenases; Disease Models, Animal; Disease Progression; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Fibroblasts; Fibrosis; GTPase-Activating Proteins; Humans; Hydralazine; Kidney; Mice; Mice, Inbred C57BL; Mice, Transgenic; Primary Cell Culture; Promoter Regions, Genetic; Proto-Oncogene Proteins; Ramipril; Renal Elimination; Renal Insufficiency, Chronic; Reperfusion Injury; Vasodilator Agents

Cardiovascular disease, including cardiac hypertrophy, is common in patients with kidney disease and can be partially attenuated using blockers of the renin-angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to the pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using a subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in the regulation of apoptosis, fibrosis, and hypertrophy. The effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132, and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of caspase-9, B cell lymphoma-2, transforming growth factor-β, fibronectin 1, collagen type 1A1, and forkhead box protein O3, which are all known to be involved in the regulation of apoptosis, fibrosis, and hypertrophy in cardiac cells while being targets for the above microRNAs. ACE inhibitor treatment increased expression of microRNA-133 and microRNA-1. The inhibitory action of ACE inhibitor treatment on increased cardiac NADPH oxidase isoform 1 expression after subtotal nephrectomy surgery suggests that inhibition of oxidative stress is also one of mechanism of ACE inhibitor-mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACE inhibition in acute renal injury, which is mediated through an inhibitory action on profibrotic and proapoptotic target genes and stimulatory action on antihypertrophic and antiapoptotic target genes.

Topics: Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cardiomegaly; Cell Line; Collagen; Cytoprotection; Disease Models, Animal; Fibrosis; Kidney; MicroRNAs; Myocytes, Cardiac; NADH, NADPH Oxidoreductases; NADPH Oxidase 1; Oxidative Stress; Ramipril; Rats, Sprague-Dawley; Signal Transduction; Superoxide Dismutase; Transforming Growth Factor beta1

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

Topics: Acute Kidney Injury; Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Body Mass Index; Cardiac Surgical Procedures; Diuretics; F2-Isoprostanes; Female; Humans; Interleukin-6; Male; Middle Aged; Obesity; Oxidative Stress; Plasminogen Activator Inhibitor 1; Postoperative Complications; Ramipril; Randomized Controlled Trials as Topic; Risk Factors; Signal Transduction; Spironolactone

Topics: Acute Kidney Injury; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Fever; Humans; Hydrotherapy; Male; Neuroleptic Malignant Syndrome; Olanzapine; Ramipril

We report a case of acute renal insufficiency in a 77 year-old patient who took flurbiprofen as antiplatelet therapy. This is an important observation because it illustrates the potential risk of acute renal insufficiency, when using flurbiprofen before invasive medical examination or surgery in patients receiving long-term treatment with angiotensin converting enzyme inhibitors or angiotensin II inhibitors. This risk is probably underestimated in usual clinical practice.

Topics: Acute Kidney Injury; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Flurbiprofen; Humans; Male; Platelet Aggregation Inhibitors; Ramipril

Numerous agents have been associated with minimal change disease. We describe a previously unreported association in a 45-year-old white woman of scuba diving exposure to fire coral (Millepora species) that was followed by the development of nephrotic syndrome, acute renal failure, pulmonary edema, and intubation. The renal biopsy specimen was consistent with minimal change disease. Institution of corticosteroid therapy resulted in symptomatic improvement and resolution of proteinuria. Physicians, particularly those in scuba-diving areas, should consider minimal change disease in exposed patients with proteinuria because a prompt diagnostic and therapeutic approach may potentially limit complications.

Topics: Acute Kidney Injury; Animals; Anthozoa; Barbados; Bites and Stings; Combined Modality Therapy; Diving; Edema; Female; Forearm Injuries; Furosemide; Humans; Hydralazine; Intubation, Intratracheal; Labetalol; Marine Toxins; Middle Aged; Mitral Valve Insufficiency; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisone; Pulmonary Edema; Ramipril

Topics: Acute Kidney Injury; Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors; Cathartics; Colitis; Humans; Nephrocalcinosis; Phosphates; Ramipril; Renal Insufficiency; Risk Factors

A 59-year-old man was referred to the hospital for psychiatric reasons. To control hypertension and chronic heart failure he had been treated with 5 mg ramipril and 12.5 mg hydrochlorothiazide. In addition, he received 25 mg spironolactone. A prostate disease was diagnosed two months ago.. Laboratory analysis revealed a severe hyperkalemia (9.3 mmol/l) as well as an increase in creatinine (24.3 mg/dl) and urea nitrogen (349.0 mg/dl). The ECG showed a bradycardia with increased T-wave amplitudes. Abdominal sonography revealed a full urinary bladder.. Administration of terbutaline, sodium bicarbonate, and glucoseinfusion lowered potassium level to 6.3 mmol/l before hemodialysis was started. Hyperplasia of the prostate gland was found to be the reason for acute renal failure. Dialysis treatment was only temporarily necessary; afterwards, the patient was transferred to the urology department for subsequent therapy.. Hyperkalemia is a life-threatening emergency that requires immediate therapy. Conservative treatment allows to partially correct water-electrolyte imbalance until hemodialysis can be performed. Hyperkalemia often results from the administration of combination therapy with ACE-inhibitors/AT (1)-antaganonists and antikaliuretic diuretics (spironolactone) in renal failure.

Topics: Acute Kidney Injury; Adrenergic beta-Agonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Bradycardia; Diuretics; Drug Therapy, Combination; Electrocardiography; Emergencies; Glucose; Heart Failure; Humans; Hydrochlorothiazide; Hyperkalemia; Hypertension; Male; Mental Disorders; Middle Aged; Prostatic Hyperplasia; Ramipril; Renal Dialysis; Sodium Bicarbonate; Terbutaline